tbuckley/cabot-search huggingface dataset:
Abstract 16082: Racial Differences Among Patients Undergoing Nuclear Myocardial Perfusion Imaging
Authors: Catherine X Wright, Erica S Spatz, Edward J Miller, Attila Feher
Journal: Circulation (2023)

Introduction: Noninvasive cardiac stress testing is valuable for early diagnosis and optimizing management of patients with coronary artery disease (CAD). Historically, Black patients have experienced both underdiagnosis and undertreatment of CAD. We evaluated racial disparities in patients undergoing nuclear myocardial perfusion imaging (MPI). Different modalities (MPI (SPECT, PET) vs. stress echocardiography) have variations in accuracy, cost and radiation exposure, which may reflect provider biases. Methods: Patient-reported demographics, clinician-reported cardiac risk factors and MPI study characteristics from a large Connecticut health system (2016 - 2022) were compared for Black and White patients in both general and matched cohorts (1:1 matched for demographics and risk factors). Results: The study included 123,069 cardiac stress tests from 10.5% Black and 76.2% White patients (largely similar to overall Connecticut population: 12.7% Black, 78.8% White). Black patients were younger (56.7±13.3 vs. 62.1±13.4 years, p&lt; 0.001), more likely female (58.7 vs. 44.7%, p&lt;0.001) and had more risk factors (Table 1). Black patients were more likely to undergo MPI (66.6 vs. 50.5%, p&lt;0.001), inpatient or observation status testing (17.0 vs. 8.4%, p&lt; 0.001), with pharmacological rather than exercise stress (53.9 vs. 37.0%, p&lt;0.001) than White patients. On analysis of the 1:1 matched cohort, Black patients younger than 65 years were more likely to undergo MPI than White patients (62.1 vs. 57.4%, p&lt;0.001), while the reverse is seen for patients over 65 years old (37.5 vs. 42.5%, p&lt;0.001). Conclusion: Significant demographic and stress testing pattern differences were found between Black and White patients. These findings may reflect racial disparities in cardiovascular care, including access and clinical referral patterns. Further studies are needed to determine if these differences in stress testing strategies impact downstream clinical outcomes.
Abstract 16096: Systolic Blood Pressure, Preeclampsia, and Leiomyoma Genes - A Multivariable Mendelian Randomization and Mediation Analysis
Authors: Nataraja Sarma Vaitinadin, Mingjian Shi, Jonathan Mosley, Ayush Giri
Journal: Circulation (2023)

Introduction: Preeclampsia (PE) (sudden-onset hypertension (&gt;20 weeks gestation) with proteinuria, maternal organ/uteroplacental dysfunction or angiogenic imbalance) affects ~4 million women annually, causing death of &gt;70,000 women and 500,000 babies, and sequelae like heart failure. Hypothesis: We hypothesize that among the known genetic associations of PE is an independent risk factor (IRF). Methods: Data Publicly available European ancestry genome-wide association study (GWAS) summary statistics (SS) derived single nucleotide polymorphism (SNP) based genetic instruments ( P- value≤5x10 -08 , r 2 &lt;0.001) for known associations of PE [body mass index (BMI, kg/m 2 ) (339,224 subjects), high density lipoprotein (HDL, mg/dl) (188,577), blood pressure BP (mm Hg) - systolic (S) and diastolic (D) (458,577)] with SS for PE or eclampsia (7212 cases, 194266 controls) (outcome). Analyses 1) univariate two-sample Mendelian randomization (MR) [inverse variance weighted method (IVWM) for results; MR-Egger, and weighted-median methods for sensitivity analyses]; 2) multivariable (MV) MR to identify IRF after MV adjustment, 3) quantify change in effect size of IRF after adjustment (results reported as odds of PE per 10 unit change in SBP/DBP/HDL, and per standard deviation (SD) change in BMI); and 4) FUMA based analysis of IRF SNPs to annotate uterine genes using GTEx v8. Results: In 1) IVWM analysis, SBP (OR= 2.23 [95% CI= 1.82, 2.72]), DBP (3.32 [2.46,4.48], HDL (0.22 [0.09,0.55]), and BMI (1.58 [1.34,1.86]) associated with the odds of a diagnosis of PE; 2) MVMR analysis, only SBP (1.82 [1.11, 3.00] remained significant, after adjustment for BMI, DBP, and HDL; 3) proportion-explained analysis, ~18% reduction in the OR of SBP, after adjustment for BMI, DBP, and HDL; and 4) in FUMA based analyses, out of 7 gene associations, the top 2 uterine genes for SBP SNPs were ZNF859 , and CDC25A . Conclusions: Genetic predisposition to elevated SBP associated with increased odds of PE, independent of BMI, DBP, and HDL. Adjustment attenuated risk, suggesting shared genetic mechanisms. SBP is an independent risk factor for PE. SBP SNPs map to uterine ZNF859 and CDC25A, known leiomyoma associated genes, suggesting a pleiotropic role in PE development.
Abstract 16947: Sotagliflozin, a Dual SGLT 1 and 2 Inhibitor, Has High Membrane Affinity and Hydrocarbon Core Location Compared With Empagliflozin
Authors: Samuel C Sherratt, Alexa V Weindorf, Peter Libby, Deepak L Bhatt, Preston Mason
Journal: Circulation (2023)

Background: The dual SGLT-1 and 2 inhibitor sotagliflozin (sota) reduced atherothrombotic events and hospitalization for worsening heart failure in patients with diabetes in clinical trials (SCORED, SOLOIST). Unlike selective SGLT2 inhibitors such as empagliflozin (empa), sota binds with higher affinity to SGLT1, which is located in the intestine, kidney, heart, brain, and vascular endothelial cells. To elucidate the physico-chemical basis for differences in tissue distribution and receptor affinity, we compared the effects of these drugs on membrane binding and molecular location. Methods: Membranes reconstituted from cardiac phospholipid and cholesterol were used to measure drug partitioning across a range of cholesterol concentrations. Multilamellar vesicles were prepared as mixtures of cardiac phospholipid (CPL), cholesterol, and each agent at 30 μM or vehicle. Drug-membrane partitioning was determined by rapid centrifugation and UV/Vis spectrophotometry. In parallel experiments, we used small angle x-ray scattering (SAXS) to identify drug location in model membranes containing phosphatidylcholine and cholesterol. Results: Sota had a membrane partition coefficient (8590 ± 2078) that was 16-fold higher than empa (519 ± 195, p&lt;0.001) in CPL membranes. This high membrane affinity was preserved over a range of cholesterol levels compared to empa (p&lt;0.001). Consistent with high membrane affinity, SAXS analysis showed that sota had a location evidenced by a broad increase in electron density in the hydrocarbon core extending to approximately 20 Å from the membrane center. By contrast, empa had a location limited to the polar headgroup region, consistent with its lower lipophilicity and tissue penetration. Conclusions: Sota had high membrane affinity and distinct location in the hydrocarbon core compared to empa. This may contribute to the effect of its dual SGLT-1 and 2 inhibition in vivo across various tissues including the heart. These distinct membrane interactions may also partially explain the reduced atherothrombotic risk as demonstrated in outcome trials with sota but not selective SGLT-2 inhibitors.
Abstract 16902: Molecular Basis of the Vascular Cell Phenotypic Switch and Wall Remodeling in Abdominal Aortic Aneurysm: NOX4 NADPH Oxidase-Derived Mitochondrial Oxidative Stress and DNA Damage
Authors: Aleksandr E Vendrov, Jamille Silveira Fernandes Chamon, Julia Levin, Takayuki Hayami, Marschall S Runge, Nageswara R Madamanchi
Journal: Circulation (2023)

Vascular cells phenotypic changes and wall remodeling are the hallmarks of abdominal aortic aneurysm (AAA) pathology. Mitochondrial oxidative stress (mtOS) is associated with the vascular smooth muscle cells (SMC) and macrophage phenotypic switch. We previously reported that NOX4 NADPH oxidase expression is increased in cardiovascular cells in response to pathological insult inducing mtOS and dysfunction and vascular disease progression. We tested the hypothesis that NOX4-dependent mtOS and DNA damage induce vascular phenotypic changes and remodeling resulting in AAA progression. In angiotensin II (Ang II)-induced AAA model Apoe -/- / Nox4 Tg mice with mitochondria-targeted overexpression of NOX4 had the highest, whereas Apoe -/- / Nox4 -/- displayed the lowest incidence of AAA, abdominal aorta area and diameter as compared with Apoe -/- mice. The aortic wall ROS levels, oxidative DNA damage and DNA damage response markers, elastin degradation index, MMP2 expression, and macrophage infiltration were significantly higher in AngII-treated Apoe -/- / Nox4 TG mice compared with Apoe -/- or Apoe -/- / Nox4 -/- mice. Spectral flow cytometry analysis of AAA cell suspension from Ang II-infused mice revealed a decrease in contractile SMCs but an increase in macrophage-like SMC populations, as well as increased number of infiltrating pro-inflammatory macrophages in Apoe -/- / Nox4 TG mice. As compared with wild-type or Nox4 -/- mice, Ang II-treated SMC from Nox4 TG mice showed significantly elevated mtOS, DNA damage, dysfunction, as well as activation of cGAS-STING pathway and NLRP3/AIM2 inflammasome expression. Flow cytometry analysis of Ang II-treated Nox4 TG mice SMC contained a lower proportion of cells with contractile markers (ACTA2 + , MYH11 + , TAGLN + ) and a higher proportion of cells with macrophage-like markers (CD68 + , CD11b + , LGALS3 + ). These data suggest that NOX4-dependent mitochondrial DNA damage and activation of DNA-sensing pathways have a causal role in AAA development, leading to macrophage-like SMCs, increased inflammation, and vessel wall remodeling. NOX4 inhibition and mitochondrial function augmentation may be beneficial in preserving aortic wall integrity in AAA-susceptible patients.
Abstract 12538: Myocardial Bridge Induced Cardiomyopathy
Authors: Bharat Marwaha, Indrajeet Mahata, Navneet Kumar, Puneet Gupta, Goldendeep Singh, Iqra Riaz
Journal: Circulation (2023)

Introduction: A myocardial bridge(MB) is a condition in which the epicardial coronary artery traverses through the myocardium, has an intra-myocardial course of varying length, and then exits the myocardium and appears on the surface of the heart. Clinical Presentation: A 54-year-old male with no significant past medical history except tobacco abuse and anxiety presented to the hospital with retrosternal chest pain radiating to the back and shoulder and associated with nausea and diaphoresis. His SBP was 100/60, and his heart rate 46. His EKG showed ST elevation in inferior leads, and he was given a nitro tablet, which improved the chest pain to 5/10. He was emergently taken to the Cath lab and found to have proximal left circumflex artery occlusion and underwent PCI with a 2.25x23 Xience Drug-eluting stent. Troponin was elevated to 2.35. His cath also showed a significant mid-LAD myocardial bridge. His echocardiogram showed mid and apical anterior, anterior septal, apical wall, and inferior wall hypokinesis. His EF has been reduced to 30%. Coronary CTA showed mid-LAD has myocardial bridging, which is more than 2 cm long and 5 mm deep in the muscle. The patient has persistently low HR in 40-45, beta-blocker was not started. Due to significant cardiomyopathy induced by a myocardial bridge, unroofing of LAD was done off-pump. His EF improved to 55% after three months of surgery. Discussion: CABG or myotomy is the treatment of choice for patients with symptomatic myocardial bridging refractory to medical therapy, evidence of myocardial ischemia or infarction, or &gt;75% systolic coronary compression on angiography. Incidental myocardial bridging finding without ischemia or symptoms does not require any treatment. Symptomatic patients with ischemia on stress tests can be offered beta or calcium channel blockers. Medical therapy is superior to revascularization with percutaneous intervention.
Abstract 19127: The Effect of Frailty on 30 Day Rate of Readmission Among Patients With N/Stemi and Spontaneous Coronary Artery Dissection
Authors: Anmol S Johal, Ndausung Udongwo, Steven Imburgio, Anton Mararenko, Viraaj Pannu, Brett Miller, Sowmya Dandu, Temidayp Abe, Hira Akhlaq, Brett Sealove, Joseph Heaton
Journal: Circulation (2023)

Introduction: Spontaneous coronary artery dissection (SCAD) can present as myocardial infarction or sudden death, particularly in young patients. SCAD is primarily diagnosed on angiography thus the majority of patients present with findings of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). Hypothesis: We sought to determine the 30-Day readmission rate (30-DRr) for STEMI/NSTEMI in frail individuals with SCAD and its impact on healthcare utilization and economic burden in the United States. Methods: Using the 2020 National Readmission Database and International Classification of Diseases, 10th revision (ICD-10) codes, a retrospective study of patient discharges with N/STEMI as a primary diagnosis and with SCAD as a secondary diagnosis. The primary outcome was 30-DRr, while secondary outcomes were readmission mortality rate, length of stay, and resource utilization defined by hospital charge (HC). Outcomes were analyzed to compare frail and non-frail individuals. Results: A total of 19,277 index hospitalizations for N/STEMI with a secondary diagnosis of SCAD were identified. The mean age on index admission was 59.53 ± 12.10 years, 57.16% (11,018) were female, and the in-hospital mortality rate was 5.84% (n = 1,125.70). There were 4,068 (21.10%) frail individuals identified. The 30-DRr was 13.30% for frail patients vs 6.51% for non-frail patients (adjusted p &lt; 0.001). There was an 18.48% in-hospital mortality for frail individuals vs 2.46% mortality for non-frail individuals (adjusted p &lt; 0.001). There were also significant increases in length of stay for frail patients, 9.58 days, vs 3.49 days for non-frail patients (adjusted p &lt; 0.001), and total HC for frail patients $61,068.09 when compared to non-frail, $25,248.12 (adjusted p &lt; 0.001). Conclusions: Frail patients with SCAD are at higher risk for readmission when compared to non-frail individuals with SCAD. The implications of this data include the possible implementation of closer follow-up with cardiology post-discharge, and need for further studies into the clinical course, interventions, and outcomes associated with SCAD.
Abstract 15602: Impact of COVID-19 on Cardiovascular Outcomes in Patients Hospitalized With Chronic Heart Failure: A Nationwide Propensity-Matched Analysis
Authors: Abhiram Challa, Tejasri Polana, Rhythm Vasudeva, Abdul Rahman R Akkawi, Mohinder Reddy Vindhyal
Journal: Circulation (2023)

Introduction: Coronavirus 19 (COVID-19) has rapidly emerged as a major contributor to hospitalizations and readmissions, with growing evidence emphasizing its correlation with adverse outcomes in heart failure (HF). This study aims to investigate the impact of COVID-19 on cardiovascular outcomes in patients hospitalized with HF. Goals: To assess the impact COVID-19 on mortality, readmissions, and other cardiovascular outcomes in HF patients. Methods: Patients &gt;18 years hospitalized with a diagnosis of chronic HF and COVID-19 were identified in the 2020 National Readmissions Database. Nearest propensity matching (PSM) was conducted using a 1:1 ratio for demographic, social, and clinical variables. PSM was repeated for systolic and diastolic heart failure subgroups. Outcomes with &lt;10 cases were excluded per HCUP rules. Results: Amongst the 1,922,680 CHF patients identified, 461 had COVID-19. Baseline characteristics are shown in Table 1. After matching, COVID-19 showed no significant impact on mortality, 30- and 90- day readmissions, acute myocardial infarction, or acute kidney injury (AKI). Interestingly, the subgroup analysis revealed that COVID-19 significantly reduced AKI in diastolic HF (Table 2). Conclusions: Patients with COVID-19 hospitalized with HF are not at a higher risk for mortality, readmissions, or other cardiovascular outcomes. Interestingly, a significant reduction in AKI was observed in diastolic HF patients with COVID-19, warranting further investigation.
Abstract 16093: Hemodynamic Implications of Transseptal Access for Ventricular Tachycardia Ablation in Patients With Left Ventricular Assist Devices
Authors: Brett Curtis, Amrish Deshmukh, John D Larson, Hamid Ghanbari, Michael Ghannam, Rakesh Latchamsetty, Frank Bogun, Jackson Liang
Journal: Circulation (2023)

Introduction: Ventricular tachycardia (VT) is common in patients with left ventricular assist devices (LVAD), and catheter ablation can be an effective treatment strategy. Although transseptal approach for LV mapping and ablation is often preferred, iatrogenic atrial septal defect (ASD) after transseptal access may theoretically result in clinically significant right-to-left shunting. The short- and long-term implications of transseptal puncture, including hemodynamic changes in LVAD patients, remain uncertain. Methods and Results: From 2013-2023, 15 LVAD patients (age 68.5±12 years; 2 women) underwent 18 VT ablation procedures with single transseptal access for LV ablation without ASD closure afterwards. Clinical VT was eliminated in 83%. No patients had prior PFO/ASD; Mean RVSP was 45mmHg, 6 (40%) had pulmonary hypertension, and 8 (53.3%) had moderate or severe RV dysfunction. All patients had previously failed at least 1 antiarrhythmic drug (amiodarone 100%; sotalol 33%; mexiletine 94%). Procedural complications occurred in 3 procedures (all related to vascular access, none directly related to transseptal access; 1 patient with interrupted IVC requiring transhepatic access had bleeding due to transection of intercostal artery requiring arterial embolization). Post-procedure echocardiograms (n=14; mean time to echo 90±116 days) showed no intra-cardiac shunting or persistent ASD. Right heart catheterization (pre: n=12; post: n=8, at mean follow-up 187±243 days) showed similar pre- and post-ablation RA pressures (11.6 vs 14.9 mmHg, p =0.24) and wedge pressures (14.9 vs 20.4 mmHg, p =0.8) with absence of significant shunting based on pre- and post-ablation arterial (95.2% vs 97.7%, p =0.06) and PA oxygen saturations (56.5% vs 51.3%, p =0.29). No episodes of clinically significant hypoxia occurred after ablation. Conclusion: Transseptal access for VT ablation can be safely performed in LVAD patients and is unlikely to result in clinically or hemodynamically significant residual shunting over long-term follow-up. Therefore, empiric ASD closure after transseptal access in all LVAD patients is likely unnecessary.
Abstract 13840: Safety Outcomes From a First-in-Human Study of a Novel Investigational Monoclonal Antibody, REGN5381, an Agonist to the Natriuretic Peptide Receptor 1
Authors: Aaron P Kithcart, Michael E Dunn, Jan de Hoon, Wouter Botermans, Satyajit Karnik, Michael E Burczynski, Wenjun Zheng, Andrew J Rankin, Gary Herman, Benjamin Olenchock
Journal: Circulation (2023)

Introduction: Natriuretic peptides (NPs) regulate vascular volume and tone via the membrane-bound guanylate cyclase, natriuretic peptide receptor 1 (NPR1). Activation of this pathway is known to lower systemic and venous blood pressure (BP) and effect natriuresis and diuresis. Previous recombinant NP infusions for heart failure were limited by their duration of effects. REGN5381, a novel investigational NPR1 agonist monoclonal antibody, showed sustained hemodynamic effects in animal models. Here, we report safety and pharmacodynamic (PD) outcomes from a phase 1, first-in-human study of REGN5381. Hypothesis: REGN5381 is sufficienty well tolerated in healthy humans to warrant continued clinical investigation. Aim: To assess the safety, tolerability, and REGN5381 PD in normotensive humans. Methods: This double-blind, single-ascending dose study (NCT04506645), randomized healthy adults aged 18-55 years (6:2) to receive a single intravenous dose of REGN5381 or placebo. Participants received a fixed-sodium and fluid diet and remained 4 days in the clinic for non-invasive hemodynamics monitoring and safety assessment. Results: A total of 48 participants were enrolled; 12 were randomized to placebo and 6 to each of 6 REGN5381 dose levels (total n=36). Eight (66.7%) participants in the placebo and 24 (66.7%) in the total REGN5381 group reported ≥1 treatment-emergent adverse event (TEAE), with no obvious relationship to dose level. Four (33.3%) participants in the placebo and 15 (41.7%) in the total REGN5381 group reported ≥1 study drug related TEAE, with no obvious relationship to dose level. Common TEAEs (experienced by &gt;10% of participants in the total group) were postural dizziness (placebo: 2 [16.7]%; total REGN5381: 6 [16.7]%) and headache (placebo: 5 [41.7%]; total REGN5381: 4 [11.1%]). Pyuria and orthostatic hypotension were reported in 4 (11.1%) participants in the total group, but none in the placebo group. No serious or severe TEAEs or deaths were reported in any dose groups. Participants treated with the highest dose saw a 7-11 mmHg reduction of systolic BP that was sustained over 72 hours (the full duration of inpatient monitoring). Conclusion: A single dose of REGN5381 is generally well-tolerated and provides sustained hemodynamic effects.
Abstract 19197: Cardiopulmonary Outcomes and Disparities in Long-Term Anticoagulant Use in Secondary Pulmonary Hypertension Patients: A Nationwide Analysis
Authors: Kavya Shankar, Ibrahim Ahmed
Journal: Circulation (2023)

Introduction: The use of anti-coagulation in pulmonary hypertension patients has shown to improve mortality. Our aim was to characterize patient demographics, analyze disparities and investigate the effect of long-term anti-coagulant (AC) use on outcomes in secondary pulmonary hypertension (PAH) patients. Methods: This was a retrospective cohort study using the 2019 Nationwide Inpatient Sample database to identify admissions in adults with diagnoses of secondary PAH and long-term AC use. Multivariate linear and logistic regression models were adjusted for demographic variables and comorbid conditions. Primary outcome was all-cause mortality, and secondary outcomes were outcomes of long-term AC use in secondary PAH patients and length of stay (LOS). Results: Out of 1,141,870 secondary PAH patients, 287,940 had long-term AC use. The AC-PAH cohort when compared to the Non-AC-PAH cohort had lower in-hospital mortality (3.35% vs 5.18%, p&lt;0.001) and shorter LOS (6.04 days vs 7.03 days, p&lt;0.001). The AC-PAH cohort had older patients (mean age 74.46 vs 69.55 years, p&lt;0.001), more White patients (73.10% vs 64.76%, p&lt;0.001) and fewer Black patients (15.62% vs 20.10%, p&lt;0.001). The AC-PAH cohort when compared to the Non-AC-PAH cohort had lower odds of pulmonary embolism (PE)(OR 0.92, 95% CI 0.86-0.98, P&lt;0.05), acute respiratory failure (RF)(OR 0.73, 95% CI 0.71-0.75, p&lt;0.001), ventilator dependence (OR 0.46, 95% CI 0.38-0.55, p&lt;0.001), systemic HTN (OR 0.91, 95% CI 0.83-0.99, p&lt;0.05), cardiac arrest (OR 0.65, 95% CI 0.59-0.72, p&lt;0.001), ischemic cardiomyopathy (OR 0.94, 95% CI 0.90-0.98, p&lt;0.005), STEMI (OR 0.31, 95% CI 0.22-0.42, p&lt;0.001), NSTEMI (OR 0.52, 95% CI 0.49-0.55, p&lt;0.001) and acute ischemic stroke (OR 0.71, 95% CI 0.66-0.77, p&lt;0.001). The AC-PAH cohort had higher odds of chronic RF (OR 1.07, 95% CI 1.02-1.12, P&lt;0.005) and atrial fibrillation (A.Fib)(OR 2.79, 95% CI 2.72-2.86, p&lt;0.001). Conclusion In secondary PAH patients, the long-term use of AC was associated with lower in-hospital mortality, shorter LOS and lower odds of having PE, acute RF, ventilator dependence, systemic HTN, ischemic cardiomyopathy, STEMI, NSTEMI and acute ischemic stroke. More extensive research is required in this area to investigate outcomes further.